N 1 -Benzylarylhydrazine compounds, their preparation methods and applications

Abstract

The present application relates to the field of organic chemistry, in particular to N 1 The present application relates to the field of organic chemistry, in particular to N 1 The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present application relates to the field of organic chemistry, in particular to N The present

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, specifically to N. 1 - Benzylarylhydrazine compounds, their preparation methods, and applications. Background Technology

[0002] N 1 Substituted arylhydrazines are not only the core skeletons of important biologically active molecules but also important synthons in organic synthesis, widely used to prepare various biologically active nitrogen-containing heterocyclic compounds. However, the methods for synthesizing these compounds are currently limited. Traditional synthetic methods utilize the diazotization of aniline with nitrous acid, a multi-step reaction requiring the use of highly toxic nitrites. Later, some nucleophilic substitution reactions were developed to synthesize N... 1 -Substituted arylhydrazine compounds, however, these reactions require large amounts of strong bases. Recently, transition metal-catalyzed N... 1 Direct functionalization is also a promising synthetic strategy; however, the involvement of transition metals can lead to metal residues in drug synthesis. Therefore, developing a simple, efficient, and mild method for constructing N... 1 The method of substituting arylhydrazine compounds has significant research value and practical application value. Summary of the Invention

[0003] Based on this, the present invention provides N 1 - Benzylarylhydrazine compounds, their preparation methods and applications, which solve at least one problem in the prior art.

[0004] In a first aspect, the present invention provides N as shown in Formula III. 1 -Benzylarylhydrazine compounds: Formula III, R and R' are independently selected from hydrogen, alkyl, and groups containing mono- or poly-substituted electron-donating and electron-withdrawing effects.

[0005] Secondly, the present invention provides N as shown in Formula III. 1 A method for preparing benzylarylhydrazine compounds, comprising the following steps: Under conditions involving triphenylphosphine (PPh3) and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), benzyl alcohol compounds of formula I and arylhydrazine compounds of formula II are reacted in a solvent to obtain N of formula III. 1 -Benzylarylhydrazine compounds; Formula I, Formula II; R and R' are independently selected from hydrogen, alkyl, and groups containing mono- or poly-substituted electron-donating and electron-withdrawing effects.

[0006] Thirdly, the present invention provides N as shown in Formula III. 1 Application of β-benzylarylhydrazine compounds in the preparation of indole compounds.

[0007] Due to the adoption of the above technical solutions, the embodiments of the present invention have at least the following beneficial effects: A series of N-type organic compounds (DDQ and PPh3) were synthesized using readily available benzyl alcohol and arylhydrazine as raw materials under metal-free and alkali-free conditions through dehydration. This process was simple, efficient, mild, and left no metal residue. 1 -Benzyl-substituted arylhydrazine compounds are used to synthesize indole compounds. The synthetic method does not require metal catalysts or bases, the raw materials are simple and readily available, the reaction route is short, the production cost is low, the reaction conditions are not harsh, and the obtained products have high purity. It is a new synthetic method that is more economical, more environmentally friendly, and has simpler and milder reaction conditions, and can be widely used in the synthesis of N-substituted indole compounds. Attached Figure Description

[0008] Figure 1 The above is the 1H NMR spectrum of compound 3aa in an embodiment of the present invention.

[0009] Figure 2 The image shows the carbon NMR spectrum of compound 3aa in an embodiment of the present invention.

[0010] Figure 3 The above is the 1H NMR spectrum of compound 3ab in an embodiment of the present invention.

[0011] Figure 4 This is the carbon NMR spectrum of compound 3ab in an embodiment of the present invention.

[0012] Figure 5 The image shows the hydrogen nuclear magnetic resonance spectrum of compound 3ac in an embodiment of the present invention.

[0013] Figure 6 This is the carbon NMR spectrum of compound 3ac in an embodiment of the present invention.

[0014] Figure 7 The above is the 1H NMR spectrum of compound 3ad in an embodiment of the present invention.

[0015] Figure 8 This is the carbon NMR spectrum of compound 3ad in an embodiment of the present invention.

[0016] Figure 9 The image shows the proton NMR spectrum of compound 3ba in this embodiment of the invention.

[0017] Figure 10 This is the carbon NMR spectrum of compound 3ba in an embodiment of the present invention.

[0018] Figure 11 The image shows the hydrogen nuclear magnetic resonance spectrum of compound 3ca in an embodiment of the present invention.

[0019] Figure 12 This is the carbon NMR spectrum of compound 3ca in an embodiment of the present invention.

[0020] Figure 13 The image shows the hydrogen nuclear magnetic resonance spectrum of compound 3da in an embodiment of the present invention.

[0021] Figure 14 This is the carbon NMR spectrum of compound 3da in an embodiment of the present invention.

[0022] Figure 15 The image shows the hydrogen nuclear magnetic resonance spectrum of compound 3ea in this embodiment of the invention.

[0023] Figure 16 This is the carbon NMR spectrum of compound 3ea in an embodiment of the present invention.

[0024] Figure 17 The image shows the hydrogen nuclear magnetic resonance spectrum of compound 3fa in an embodiment of the present invention.

[0025] Figure 18 This is the carbon NMR spectrum of compound 3fa in an embodiment of the present invention.

[0026] Figure 19 The image shows the hydrogen nuclear magnetic resonance spectrum of compound 3ga in an embodiment of the present invention.

[0027] Figure 20 This is the carbon NMR spectrum of compound 3ga in an embodiment of the present invention.

[0028] Figure 21 The image shows the hydrogen nuclear magnetic resonance spectrum of compound 3ha in an embodiment of the present invention.

[0029] Figure 22 This is the carbon NMR spectrum of compound 3ha in an embodiment of the present invention.

[0030] Figure 23 The above is the 1H NMR spectrum of compound 4a in an embodiment of the present invention.

[0031] Figure 24 This is the carbon NMR spectrum of compound 4a in an embodiment of the present invention. Detailed Implementation

[0032] The following will provide a clear and complete description of the concept and technical effects of the present invention, so as to fully explain the purpose, solution and effects of the present invention.

[0033] This invention uses benzyl alcohol (primary alcohol) and arylhydrazine as starting materials, and constructs a series of N-containing compounds through the dehydration of DDQ and PPh3. 1 This invention relates to benzylarylhydrazine compounds and their application in the synthesis of indole compounds. The advantages of this synthetic method include simple and readily available reactants, simple, mild, and efficient reaction conditions with no metal residue issues, conforming to the principles of green chemistry. Furthermore, this reaction can efficiently synthesize indole compounds, showing great promise for a wide range of applications. This invention will provide a more environmentally friendly route for the synthesis of indole drug molecules.

[0034] The N 1 -Benzylarylhydrazine compounds have the structure shown in Formula III: Formula III, R and R' are independently selected from hydrogen, alkyl, and groups containing mono- or poly-substituted electron-donating and electron-withdrawing effects.

[0035] In some optional embodiments, R and R' are independently selected from hydrogen, C1-C2, C2-C3, C4-C4, C5-C6 ... 18 Alkyl, C1-C 18 The R and R' are alkoxy, phenyl, naphthyl, morpholinyl, halogen atom, phenylthio, and pyrazolyl groups. Preferably, the R and R' are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, phenyl, naphthyl, morpholinyl, fluorine, chlorine, bromine, iodine, phenylthio, and pyrazolyl groups.

[0036] In some alternative embodiments, the N 1 -Benzylarylhydrazine compounds are one of the compounds shown in the following formulas: .

[0037] The N 1 The preparation method of benzylarylhydrazine compounds includes the following steps: Under conditions involving triphenylphosphine (PPh3) and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), benzyl alcohol compounds of formula I and arylhydrazine compounds of formula II are reacted in a solvent to obtain N of formula III. 1-Benzylarylhydrazine compounds; The definitions of R and R' are the same as those above.

[0038] This method uses arylhydrazine compounds and benzyl alcohol compounds as starting materials to construct N through a simple thermal reaction via the PPh3-DDQ dehydration method. 1 -Benzyl-substituted arylhydrazine compounds, compared to existing N 1 The synthesis method of benzyl-substituted arylhydrazine compounds does not require metal catalysts or bases, uses simple and readily available raw materials, has a short reaction route, is convenient to operate, has low production costs, and does not require harsh reaction conditions (it can be operated under normal pressure and requires simple equipment). Moreover, the target product is easy to purify, has good yield, and high product purity. It is a new synthetic method that is more economical, more environmentally friendly, and has simpler and milder reaction conditions.

[0039] In some optional embodiments, the arylhydrazine compound represented by Formula II is phenylhydrazine, p-tert-butylphenylhydrazine, p-bromophenylhydrazine, 2,4-dimethylphenylhydrazine, or p-methylphenylhydrazine. The arylhydrazine compounds used all have the advantages of being widely available, inexpensive, and having diverse structural types.

[0040] In some optional embodiments, the benzyl alcohol compounds represented by Formula I are p-phenylbenzyl alcohol, p-methoxybenzyl alcohol, p-chlorobenzyl alcohol, p-methylbenzyl alcohol, p-tert-butylbenzyl alcohol, and p-bromobenzyl alcohol. Using benzyl alcohol as a raw material results in relatively mild reactivity and the raw material is inexpensive and readily available.

[0041] In some optional embodiments, the molar ratio of the arylhydrazine compound of Formula II to the benzyl alcohol compound of Formula I is (1-3):1. Preferably, the molar ratio of the arylhydrazine compound of Formula II to the benzyl alcohol compound of Formula I is 3:1; at this ratio, the reaction of the raw material benzyl alcohol can be ensured to be complete, thereby improving the yield of the target product.

[0042] In some optional embodiments, the solvent is petroleum ether, dichloromethane, acetonitrile, or ethyl acetate.

[0043] In some alternative embodiments, the reaction is carried out in an oxygen, air, or nitrogen atmosphere.

[0044] In some alternative embodiments, the reaction is carried out at 0°C-80°C.

[0045] The N 1 -Benzylarylhydrazine compounds are an important class of scaffold materials, widely found in bioactive natural products and drug molecules, and are a crucial component of N-substituted indoles in organic synthesis. Therefore, the N... 1-Benzylarylhydrazine compounds can be used to prepare indole compounds. For example, in the presence of acetic acid, the N... 1 -Benzylarylhydrazine compounds and ketone compounds can react in solvents to give indole compounds.

[0046] The following are some typical examples.

[0047] Example 1: A kind of N 1 The preparation method of benzyl-substituted arylhydrazine compounds includes the following steps: In a clean 50 mL round-bottom flask, 117.9 mg of triphenylphosphine, 204.3 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under nitrogen protection, 2.0 mL of dichloromethane was added, and the mixture was stirred at room temperature. After 1 minute, 97.2 mg of phenylhydrazine and 32.4 mg of benzyl alcohol were added, and the reaction was carried out for 30 minutes under the same conditions. The reaction was monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a yellow oily liquid with a yield of 82%.

[0048] The NMR and high-resolution mass spectrometry data of compound 3aa are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.28(dq, J = 15.9, 7.4 Hz, 7H), 7.08 (d, J = 8.0 Hz, 2H), 6.80 (t, J = 7.1 Hz,1H), 4.57 (s, 2H), 3.49 (s, 2H). (e.g. Figure 1 (As shown); 13 C NMR (101 MHz, CDCl3) δ 151.8, 137.6, 129.1, 128.7, 127.9, 127.4, 118.6, 113.7, 60.4. (e.g.) Figure 2 (As shown); HRMS (ESI) m / z calcd for C 13 H 14 N2 + [M + H] + : 199.1230, found: 199.1229.

[0049] Example 2: A kind of N 1 -Benzyl-substituted arylhydrazine compounds are prepared by the following steps: In a clean 50 mL round-bottom flask, 235.8 mg of triphenylphosphine, 204.3 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under oxygen protection, 2.0 mL of petroleum ether was then added, and the mixture was stirred at 60 °C for 3 minutes. Afterward, 109.8 mg of p-methylphenylhydrazine and 32.4 mg of benzyl alcohol were added, and the reaction was continued for another 3 minutes under the same conditions. The reaction mixture was monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a yellow oily liquid with a yield of 57%. The NMR and high-resolution mass spectrometry data of compound 3ab are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.29 (ddt, J = 19.8, 14.2, 7.2 Hz, 5H), 7.07 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 2H), 4.51 (s, 2H), 3.45 (s, 2H), 2.27 (s, 3H). (e.g.) Figure 3 (As shown); 13 C NMR (151 MHz, CDCl3) δ 149.8, 137.7, 129.6, 128.7, 128.2, 128.1, 127.4, 114.2, 61.1, 20.4. (e.g.) Figure 4 (As shown); HRMS (ESI) m / z calcd for C 14 H 16 N2 + [M + H] + : 213.1386, found 213.1395.

[0050] Example 3: A kind of N 1 -Benzyl-substituted arylhydrazine compounds are prepared by the following steps: In a clean 50 mL round-bottom flask, 235.8 mg of triphenylphosphine, 204.3 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Then, under air, 2.0 mL of acetonitrile was added, and the mixture was stirred at 30 °C for 3 minutes. Afterward, 124.2 mg of p-methoxyphenylhydrazine and 32.4 mg of benzyl alcohol were added, and the reaction was continued for another 3 minutes under the same conditions. The reaction mixture was monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a black liquid with a yield of 72%. The NMR and high-resolution mass spectrometry data of compound 3ac are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.36 –7.25 (m, 5H), 7.07 (d, J = 9.0 Hz, 2H), 6.84 (d, J = 9.0 Hz, 2H), 4.43 (s, 2H), 3.77 (s, 3H), 3.25 (s, 2H). (e.g.) Figure 5 (As shown); 13 C NMR (151 MHz, CDCl3) δ 153.4, 146.4, 137.5, 128.6, 128.4, 127.5, 116.4, 114.4, 62.4, 55.7. (e.g.) Figure 6 (As shown); HRMS (ESI) m / z calcd for C 14 H 16 N2O + [M + H] + : 251.1155, found 251.1182.

[0051] Example 4: A kind of N 1 -Benzyl-substituted arylhydrazine compounds are prepared by the following steps: In a clean 50 mL round-bottom flask, 235.8 mg of triphenylphosphine, 102.1 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under nitrogen protection, 2.0 mL of acetonitrile was added, and the mixture was stirred at 80 °C for 30 minutes. Then, 147.6 mg of p-tert-butylphenylhydrazine and 32.4 mg of benzyl alcohol were added, and the reaction was carried out for 3 minutes under the same conditions. The reaction was monitored by TLC. After the reaction was completed, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a black solid with a yield of 28%.

[0052] The NMR and high-resolution mass spectrometry data of compound 3ad are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.36 –7.26 (m, 7H), 7.04 (d, J = 8.8 Hz, 2H), 4.54 (s, 2H), 3.51 (s, 2H), 1.30 (s,9H). (such as Figure 7 (As shown); 13 C NMR (101 MHz, CDCl3) δ 149.6, 141.5, 137.9, 128.7, 128.0, 127.3, 125.9, 113.6, 60.9, 33.9, 31.5. (e.g.) Figure 8 (As shown); HRMS (ESI) m / z calcd for C 17 H 22 N2 + [M + H] + : 255.1856, found 255.1862.

[0053] Example 5: A kind of N 1 -Benzyl-substituted arylhydrazine compounds are prepared by the following steps: In a clean 50 mL round-bottom flask, 235.8 mg of triphenylphosphine, 102.1 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Then, under air, 2.0 mL of ethyl acetate was added, and the mixture was stirred at room temperature. After 30 minutes, 124.2 mg of phenylhydrazine and 36.6 mg of p-methylbenzyl alcohol were added, and the reaction was carried out under the same conditions for 1 hour and 1 minute, monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a yellow oily liquid with a yield of 67%. The NMR and high-resolution mass spectrometry data of compound 3ba are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J =7.9 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 6.88 (s, 2H), 6.80 (t, J = 7.2 Hz, 1H), 4.49 (s, 2H), 3.87 – 3.83 (m, 4H), 3.47 (s, 2H), 3.16– 3.11 (m, 4H). (e.g.) Figure 9 (As shown); 13 C NMR (101 MHz, CDCl3) δ 151.9, 150.7, 129.1, 129.0, 128.6, 118.6, 115.8, 114.0, 66.9, 59.9, 49.4. (e.g.) Figure 10 (As shown); HRMS (ESI) m / z calcd for C 14 H 16 N2 + [M + H] + : 235.1205, found 235.1202.

[0054] Example 6: A kind of N 1 The preparation method of benzyl-substituted arylhydrazine compounds includes the following steps: In a clean 50 mL round-bottom flask, 78.6 mg of triphenylphosphine, 102.1 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under nitrogen protection, 2.0 mL of ethyl acetate was added, and the mixture was stirred at 0 °C. After 1 hour, 124.2 mg of phenylhydrazine and 55.2 mg of p-phenylbenzyl alcohol were added, and the reaction was carried out for 3 minutes under the same conditions. The reaction mixture was monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a yellow solid with a yield of 72%. The NMR and high-resolution mass spectrometry data of compound 3ca are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.56 (t, J =7.7 Hz, 4H), 7.46 – 7.23 (m, 7H), 7.10 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.3 Hz, 1H), 4.61 (s, 2H), 3.57 (s, 2H). (Results) Figure 11 (As shown); 13 C NMR (101 MHz, CDCl3) δ 151.8, 140.8, 140.4, 136.7, 129.2, 128.8, 128.4, 127.5, 127.3, 127.1, 118.7, 113.7, 60.1. (Results) Figure 12 (As shown); HRMS (ESI) m / z calcd for C 19 H 18 N2 + [M + H] + : 275.1543, found 275.1546.

[0055] Example 7: A kind of N 1 The preparation method of benzyl-substituted arylhydrazine compounds includes the following steps: In a clean 50 mL round-bottom flask, 235.8 mg of triphenylphosphine, 204.3 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under oxygen atmosphere, 2.0 mL of petroleum ether was then added, and the mixture was stirred at 30 °C for 30 minutes. Afterward, 124.2 mg of phenylhydrazine and 57.9 mg of 4-morpholinobenzyl alcohol were added, and the reaction was continued for another 30 minutes under the same conditions. The reaction mixture was monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a black solid with a yield of 51%.

[0056] The NMR and high-resolution mass spectrometry data of compound 3da are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.25 (t, J =7.9 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 7.11 (d, J = 8.1 Hz, 2H), 6.88 (s, 2H), 6.80 (t, J = 7.2 Hz, 1H), 4.49 (s, 2H), 3.87 – 3.83 (m, 4H), 3.47 (s, 2H), 3.16– 3.11 (m, 4H). (e.g.) Figure 13 (As shown); 13 C NMR (101 MHz, CDCl3) δ 151.9, 150.7, 129.1, 129.0, 128.6, 118.6, 115.8, 114.0, 66.9, 59.9, 49.4. (e.g.) Figure 14 (As shown); HRMS (ESI) m / z calcd for C 17 H 21 N3O + [M + H] + : 284.1758, found 284.1764.

[0057] Example 8: A kind of N 1 The preparation method of benzyl-substituted arylhydrazine compounds includes the following steps: In a clean 50 mL round-bottom flask, 235.8 mg of triphenylphosphine, 204.3 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under nitrogen protection, 2.0 mL of ethyl acetate was added, and the mixture was stirred at 60 °C for 3 minutes. Then, 124.2 mg of phenylhydrazine and 42.6 mg of p-chlorobenzyl alcohol were added, and the reaction was carried out for 30 minutes under the same conditions. The reaction was monitored by TLC. After the reaction was completed, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a black solid with a yield of 86%.

[0058] The NMR and high-resolution mass spectrometry data of compound 3ea are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.32 –7.22 (m, 6H), 7.05 (d, J = 7.9 Hz, 2H), 6.83 (t, J = 7.3 Hz, 1H), 4.56 (s, 2H), 3.56 (s, 2H). (e.g.) Figure 15 (As shown); 13 C NMR (151 MHz, CDCl3) δ 151.6, 136.3, 133.1, 129.2, 129.2, 128.8, 118.9, 113.6, 59.8. (e.g.) Figure 16 (As shown); HRMS (ESI) m / z calcd for C 13 H 13 N2Cl+ [M + H]+ : 233.0840, found 233.0845.

[0059] Example 9: A kind of N 1 The preparation method of benzyl-substituted arylhydrazine compounds includes the following steps: In a clean 50 mL round-bottom flask, 235.8 mg of triphenylphosphine, 204.3 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under nitrogen protection, 2.0 mL of ethyl acetate was added, and the mixture was stirred at 60 °C for 30 minutes. Then, 124.2 mg of phenylhydrazine and 64.8 mg of p-phenylthiobenzyl alcohol were added, and the reaction was carried out for 3 minutes under the same conditions. The reaction was monitored by TLC. After the reaction was completed, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a yellow oily liquid with a yield of 72%.

[0060] The NMR and high-resolution mass spectrometry data of compound 3fa are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.36 –7.32 (m, 2H), 7.31 – 7.19 (m, 9H), 7.09 – 7.00 (m, 2H), 6.81 (t, J = 7.3 Hz, 1H), 4.55 (s, 2H), 3.56 (s, 2H). (e.g.) Figure 17 (As shown); 13 C NMR (151 MHz, CDCl3) δ 151.6, 136.8, 135.7, 134.8, 131.3, 131.1, 129.2, 129.1, 128.7, 127.1, 118.7, 113.5, 59.9. (e.g.) Figure 18 (As shown); HRMS (ESI) m / z calcd for C 19 H 18 N2S + [M + H] + : 307.1264, found307.1258.

[0061] Example 10: A kind of N 1 The preparation method of benzyl-substituted arylhydrazine compounds includes the following steps: In a clean 50 mL round-bottom flask, 176.9 mg of triphenylphosphine, 102.1 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Then, under air, 2.0 mL of petroleum ether was added, and the mixture was stirred at room temperature for 30 minutes. Afterward, 124.2 mg of phenylhydrazine and 55.8 mg of p-bromobenzyl alcohol were added, and the reaction was continued for another 30 minutes under the same conditions. The reaction mixture was monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a black liquid with a yield of 69%.

[0062] The NMR and high-resolution mass spectrometry data of compound 3ga are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 8.3 Hz, 2H), 7.29 – 7.24 (m, 2H), 7.18 (d,J = 8.2 Hz, 2H), 7.04 (d, J = 8.0Hz, 2H), 6.83 (t, J = 7.3 Hz, 1H), 4.54 (s, 2H), 3.59 (s, 2H). (e.g.) Figure 19 (As shown); 13 CNMR (151 MHz, CDCl3) δ 151.6, 136.8, 131.8, 129.6, 129.2, 121.2, 118.9, 113.6, 59.8. (e.g.) Figure 20 (As shown); HRMS (ESI) m / z calcd for C 13 H 13 N2Br + [M + H] + : 277.0335, found 277.0332.

[0063] Example 11: A kind of N 1 The preparation method of a benzyl-substituted arylhydrazine compound includes the following steps: In a clean 50 mL round-bottom flask, 176.9 mg of triphenylphosphine, 68.1 mg of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), and a stir bar were added. Under air, 2.0 mL of ethyl acetate was added, and the mixture was stirred at room temperature. After 30 minutes, 124.2 mg of phenylhydrazine and 52.2 mg of 4-pyrazole-1-ylbenzyl alcohol were added, and the reaction was carried out for 3 minutes under the same conditions. The reaction was monitored by TLC. After the reaction was complete, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the target product. The target product was a black solid with a yield of 78%. The NMR and high-resolution mass spectrometry data of compound 3ha are as follows: 1 H NMR (600 MHz, CDCl3) δ 7.89 (d, J =2.4 Hz, 1H), 7.71 (d, J = 1.4 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.37 (d, J = 8.4Hz, 2H), 7.29 – 7.24 (m, 2H), 7.08 (d, J= 8.1 Hz, 2H), 6.83 (t, J = 7.3 Hz, 1H), 6.47 – 6.42 (m, 1H), 4.60 (s, 2H), 3.61 (s, 2H). (e.g.) Figure 21 (As shown); 13 C NMR (151 MHz, CDCl3) δ 151.6, 141.1, 139.5, 136.0, 129.2, 129.0, 126.8, 119.5, 118.8, 113.7, 107.6, 59.9. (e.g.) Figure 22 (As shown); HRMS (ESI) m / z calcd for C 13 H 14 N2 + [M + Na] + :287.1267, found 287.1271.

[0064] Example 12: This embodiment utilizes the N prepared in Example 1. 1 A benzyl-substituted arylhydrazine compound 3aa was synthesized into an indole compound 4a, the preparation method of which includes the following steps: 29.4 mg of cyclohexanone and a stir bar were added to a 50 mL round-bottom flask, followed by 60 mg of 3aa. The mixture was stirred at 70 °C, and 2.5 mL of acetic acid was added. The reaction was carried out under these conditions for 12 hours, and the reaction was monitored by TLC. After the reaction was completed, the reaction solution was diluted with water and extracted three times with ethyl acetate. The organic layer was concentrated and separated by column chromatography to obtain the pure target product 4a, a colorless oily liquid with a yield of 84%.

[0065] The NMR and high-resolution mass spectrometry data of compound 4a are as follows: 1 H NMR (400 MHz, CDCl3) δ 7.77 – 7.63(m, 1H), 7.47 – 7.33 (m, 4H), 7.32 – 7.24 (m, 2H), 7.20 – 7.12 (m, 2H), 5.36(s, 2H), 2.95 (t, J = 5.7 Hz, 2H), 2.78 (t, J = 5.8 Hz, 2H), 2.14 – 1.98 (m,4H); 13 C NMR (101 MHz, CDCl3) δ138.5, 136.8, 135.7, 128.8, 127.7, 127.3, 126.3, 120.9, 119.0, 117.9, 110.0, 109.1, 46.3, 23.4, 23.4, 22.3, 21.3. (e.g.) Figure 24 (As shown); HRMS (ESI) m / z calcd for C 19 H 19 N + [M + H] + 262.1590, found 262.1603. In summary, the target product prepared by the method of this invention has high purity and a yield of 51%-86%, with compounds 3aa and 3ea showing the highest yields (reaching 86%). Furthermore, using these compounds as raw materials, the yield of indole compound 4a reaches 84%, further demonstrating the high purity and high conversion rate of the target product prepared by this invention. Examples 1-11 show the N prepared... 1 Benzyl-substituted arylhydrazine compounds can all be used in the organic synthesis of N-substituted indoles.

[0066] The above description is merely a preferred embodiment of the present invention. The present invention is not limited to the above-described embodiments. Any embodiment that achieves the technical effects of the present invention by the same or equivalent means should fall within the protection scope of the present invention. Within the protection scope of the present invention, various modifications and variations can be made to the technical solutions and / or implementation methods.

Claims

1. N 1 A method for preparing β-benzylarylhydrazine compounds, characterized in that, Includes the following steps: Under conditions involving triphenylphosphine and 2,3-dichloro-5,6-dicyanobenzoquinone, benzyl alcohol compounds of formula I and arylhydrazine compounds of formula II are reacted in a solvent to obtain N of formula III. 1 -Benzylarylhydrazine compounds; Wherein, R and R' are independently selected from hydrogen, C1-C 18 Alkyl, C1-C 18 The alkoxy, phenyl, naphthyl, morpholino, halogen atom, phenylthio, and pyrazolyl groups.

2. The method according to claim 1, characterized in that, The R and R' are independently selected from hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, methoxy, ethoxy, phenyl, naphthyl, morpholino, fluorine, chlorine, bromine, iodine, phenylthio, and pyrazolyl.

3. The method according to claim 1, characterized in that, The N 1 -Benzylarylhydrazine compounds are one of the compounds shown in the following formulas: 。 4. The method according to claim 1, characterized in that, The molar ratio of the arylhydrazine compound shown in Formula II to the benzyl alcohol compound shown in Formula I is (1-3):

1.

5. The method according to claim 1, characterized in that, The solvent is petroleum ether, dichloromethane, acetonitrile, or ethyl acetate.

6. The method according to claim 1, characterized in that, The reaction is carried out in an oxygen, air, or nitrogen atmosphere.

7. The method according to claim 1, characterized in that, The reaction was carried out at 0℃-80℃.

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